Journal of Neurogastroenterology and Motility : eISSN 2093-0887 / pISSN 2093-0879

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Fig. 4. Stepwise events involved in stress induced localized inflammation and barrier dysfunction. ➊ Stress induced autonomic nerve stimulation, release of peripheral corticotropin-releasing factor (CRF) and muscularis macrophages receptors activation, further strengthened by damage associated molecular patterns (DAMPs) mediated immune cells activation. ➋ Nuclear activation and release of pro-inflammatory chemokines and cytokines. ➌ Upregulation of intercellular adhesion molecules-1 (ICAM-1) in the endothelial cells of blood vessels. ➍ Influx of leukocytes in the muscularis. ➎ Increase synthesis of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes in the muscularis resident macrophages, release of inflammatory substances (prostaglandins [PGs] and nitric oxide [NO]) in the muscularis to cause localized inflammation. ➏ Mast cell and cortisol mediated barrier disruption cause translocation of luminal antigens (lipopolysaccharide [LPS]). ➐ LPS induce pathogen associated molecular patterns (PAMPs) mediated activation of mucosal immune cells to further exacerbate inflammation. ➑ The luminal antigen drainage through lymphatics and activation of dendritic cells along activation of inhibitory sympathetic and vagal nerve cause generalized inflammation through gastrointestinal tract to induce post-operative ileus. Th, T helper cells; MM, muscularis macrophages; MCP-1, monocyte chemoattractant protein-1; MIP-1α, macrophage inflammatory protein-1α; SM, smooth muscle; LM, longitudinal muscle.
J Neurogastroenterol Motil 2022;28:517~530
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